Genetics Linked to Abnormal Alzheimer's Markers

Family history of late-onset Alzheimer's disease associated with abnormal cerebral markers

FRIDAY, April 19 (HealthDay News) -- Individuals with a family history of late-onset Alzheimer's disease who are cognitively normal or mildly impaired have a higher prevalence of abnormal cerebral markers, according to a study published online April 17 in PLOS ONE.

Erika J. Lampert, from Duke University in Durham, N.C., and colleagues examined the association between a family history of late-onset Alzheimer's disease, levels of markers in cerebrospinal fluid (beta-amyloid [Aβ] 42, t-tau, and the ratio of t-tau to Aβ42), and hippocampal volume as determined by magnetic resonance imaging. Two hundred fifty-seven subjects (55 to 89 years old) classified as cognitively normal, mild cognitive impairment, or Alzheimer's disease were assessed.

The researchers found that among those with mild cognitive impairment, having a positive family history was associated with significantly lower Aβ42, significantly higher t-tau, and a significantly higher ratio of t-tau to Aβ42. Family history remained significant even after adjusting for ApoE4. Among cognitively normal subjects, 47 percent of those with a positive family history had a t-tau to Aβ42 ratio regarded as a pathologic signature of Alzheimer's disease, compared with only 21 percent of those with a negative family history. Family history was not associated with hippocampal or intracranial volumes.

"A positive family history of late-onset Alzheimer's disease is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in mild cognitive impairment," Lampert and colleagues conclude. "The unexplained genetic heritability in family history is about half the size of the ApoE4 effect."

The Alzheimer's Disease Neuroimaging Initiative is funded in part by the pharmaceutical industry. One author is on the advisory board of Janssen Alzheimer Immunotherapy.